The objective of this research program is to chemically modify anti-cancer drugs of current interest so that they are inactive unless locally activated by the proteases plasmin or plasminogen activator, which have been reported to be elevated in many tumors. Since a great deal is known about the specificity of these fibrinolytic enzymes, it should be possible to design these pro-drugs so that they are activated predominantly by the target enzymes. Since the free drugs are active predominantly against replicating cells, the pro-drugs we synthesize should be active predominantly against cells which are both replicating and producing plasminogen activator (Plasmin). By thus narrowing the target population sensitive to our drugs, we hope to decrease the toxicity of these anti-cancer drugs and thus increase their therapeutic effectiveness.